The development of new antiviral agents is an important and difficult task. In general, compared to other classes of anti-infectives, there are fewer drugs available in the field of antiviral therapy. This is due primarily to features characteristic of viral replication, which occur inside the infected cell and utilizes the cells' molecular machinery. Therefore, there are very few strategies of therapeutic intervention available that do not affect normal cells while simultaneously hindering viral infection. In addition, viral strains resistant to therapy are rapidly emerging, making the available arsenal of drugs significantly less efficient. Some widespread viral diseases (such as hepatitis C, hemorrhagic fever induced by flaviviruses Ebola, Lassa and related viruses) are virtually untreatable. Moreover, a number of new and emerging viral agents refractory to conventional treatment (such as HIV, West Nile encephalitis, hantavirus) have entered the population in recent decades and this trend is likely to continue. Therefore, antiviral agents against one or several viruses would be of immense import to the medical community.
The situation that exists in the field of HIV-induced acquired immunodeficiency syndrome (AIDS) is best known and well publicized. This epidemic started approximately twenty years ago. Currently, there are 36.1 million AIDS cases worldwide with an estimated 5.3 million new HIV infections being reported in the year 2000; the majority of infected individuals reside in the Third World. AIDS, if left untreated, will lead to the death of over 95% of infected individuals within 10 years post-infection.
There is currently no effective vaccine against HIV, notwithstanding concerted scientific and political efforts. Unfortunately, even in the best-case scenario, the generation of a safe and effective HIV vaccine along with its delivery to the population will take at least several years. Further, the most efficient vaccine will not eliminate infection from millions of affected individuals, which will need to rely on various modes of HIV treatment. Therefore, the development of any novel and cost-effective HIV drug will have enormous medical and political significance.
The only major positive development in this field has been a recent formulation of triple-drug therapy, in which patients receive a combination of three different drugs targeting either reverse transcriptase or protease. Earlier modes of monotherapy did not contain the virus for any significant period of time, resulting in the rapid generation of drug-resistant strains and ultimate disease progression. In triple-drug therapy, the virus' proclivity toward mutation is attenuated since drug-induced evolutionary pressure is applied to three different regions of the virus. Thus, these changes are not selected as rapidly (if at all) as in the case when only one drug is administered.
However, while somewhat successful, triple-drug therapy is not without limitations. First, it requires that patients thoroughly follow the drug regimen and are totally compliant therewith. Even a short discontinuation of therapy might result in virus re-emergence. Second, a patients' quality of life is impaired due to various drug-related toxic side effects. And, perhaps most importantly, the cost of these necessary drugs makes them virtually unavailable to the majority of infected individuals (including those outside of health insurance nets of the industrialized world), despite recent political efforts to the contrary. Those efforts, even if they ultimately result in a dramatic slashing of drug prices, will not be able to overturn the tide of the present epidemic, since in the foreseeable future the state of public health systems in the Third World will not provide thorough AIDS diagnostics, drug distribution and monitoring of patients' compliance.
Currently, there are no drugs effective against multiple viral agents. There is an immediate need for a class of therapeutics that can effectively eliminate virulent viruses while at the same time not exerting a toxic profile as to render them unusable.